BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models.

The protection afforded by acellular pertussis vaccines wanes over time, and there is a need to develop improved vaccine formulations. Options to improve the vaccines involve the utilization of different adjuvants and administration via different routes. While intramuscular (IM) vaccination provides a robust systemic immune response, intranasal (IN) vaccination theoretically induces a localized immune response within the nasal cavity. In the case of a Bordetella pertussis infection, IN vaccination results in an immune response that is similar to natural infection, which provides the longest duration of protection. Current acellular formulations utilize an alum adjuvant, and antibody levels wane over time. To overcome the current limitations with the acellular vaccine, we incorporated a novel TLR4 agonist, BECC438b, into both IM and IN acellular formulations to determine its ability to protect against infection in a murine airway challenge model. Following immunization and challenge, we observed that DTaP + BECC438b reduced bacterial burden within the lung and trachea for both administration routes when compared with mock-vaccinated and challenged (MVC) mice. Interestingly, IN administration of DTaP + BECC438b induced a Th1-polarized immune response, while IM vaccination polarized toward a Th2 immune response. RNA sequencing analysis of the lung demonstrated that DTaP + BECC438b activates biological pathways similar to natural infection. Additionally, IN administration of DTaP + BECC438b activated the expression of genes involved in a multitude of pathways associated with the immune system. Overall, these data suggest that BECC438b adjuvant and the IN vaccination route can impact efficacy and responses of pertussis vaccines in pre-clinical mouse models.

Imaging Cerebral Blood Vessels Using Near-Infrared Optical Tomography: A Simulation Study.

Cerebral veins have received increasing attention due to their importance in preoperational planning and the brain oxygenation measurement. There are different modalities to image those vessels, such as magnetic resonance angiography (MRA) and recently, contrast-enhanced (CE) 3D gradient-echo sequences. However, the current techniques have certain disadvantages, i.e., the long examination time, the requirement of contrast agents or inability to measure oxygenation. Near-infrared optical tomography (NIROT) is emerging as a viable new biomedical imaging modality that employs near infrared light (650-950 nm) to image biological tissue. It was proven to easily penetrate the skull and therefore enables the brain vessels to be assessed. NIROT utilizes safe non-ionizing radiation and can be applied in e.g., early detection of neonatal brain injury and ischemic strokes. The aim is to develop non-invasive label-free dynamic time domain (TD) NIROT to image the brain vessels. A simulation study was performed with the software (NIRFAST) which models light propagation in tissue with the finite element method (FEM). Both a simple shape mesh and a real head mesh including all the segmented vessels from MRI images were simulated using both FEM and a hybrid FEM-U-Net network, we were able to visualize the superficial vessels with NIROT with a Root Mean Square Error (RMSE) lower than 0.079.

Habituation of changed acoustics properties after canal wall down mastoidectomy.

PURPOSE: Our objective is to evaluate the effect of habituation on the altered ear canal acoustics after canal wall down mastoidectomy. METHODS: A total of 11 participants with single sided dry cavities and normal contralateral ear canals with normal hearing thresholds were included in the study. Filtered sound fragments were created that simulate the different acoustic properties based on the participants Real Ear to Coupler Difference (RECD) of the cavity ear and the contralateral normal ear canal. These filtered sound fragments are presented to the cavity ear canal and the contralateral normal ear canal using inserts earphones. Participants performed a subjective quality assessment of the sound fragments using paired comparison with a seven-point scale (- 3 till + 3). RESULTS: Mean assessment of sound quality revealed the following results; naturalness of sounds of the cavity ear canal is 0.29 (± 1.41; ns) in favour of the filtered sound fragment of the normal ear canal. Mean assessment of sharpness of sounds in the cavity ear canal is 1.55 (± 1.21, p = 0.55) in favour of the filtered sound fragment of the normal ear canal. Overall preference in the cavity ear canal was in favour of the normal ear canal acoustics 0.72 (SD ± 1.54 p = 0.224). CONCLUSIONS: Patients with cavity ear canals seem to habituate to their altered ear canal acoustics. Transforming the ear canal acoustics of the cavity ear to normal ear canal acoustics seem to sharpen the incoming sounds. Overall assessment of quality of sound of the normal ear canal acoustics is better than the cavity acoustics.

Evaluation of the masking efficacy of caries infiltration in post-orthodontic initial caries lesions: 1-year follow-up.

OBJECTIVES: This study aimed to qualitatively and quantitatively assess the masking efficacy and color stability of resin infiltration on post-orthodontic ICL after 1 year. MATERIALS AND METHODS: In 17 adolescents, 112 ICL (ICDAS-1: n = 1; ICDAS-2: n = 111) in 112 teeth were treated by resin infiltration (Icon, DMG) 3 to 12 months after bracket removal. The etching procedure was performed up to 3 times. Standardized digital images were taken before treatment (T0), 7 days (T7) and 12 months (T365) after treatment. Outcomes included the evaluation of the color differences between infiltrated and healthy enamel at T0, T7, and T365 by quantitative (colorimetric analysis (ΔE), ICDAS scores) and qualitative methods (5-point Likert scale (deteriorated (1), unchanged (2), improved, but not satisfying (3), improved and no further treatment required (4), completely masked (5)).) Differences between time points were analyzed by using Friedman test (ΔΕ) and chi-square tests (ICDAS). RESULTS: The median color difference (25th/75th percentiles) between carious and healthy enamel at baseline (ΔΕ0) was 10.2(7.7/13.6). A significant decrease was observed 7 days after treatment (ΔΕ7 = 3.1(1.8/5.0); p < 0.001; ICDAS; p < 0.001). No significant changes based on ΔΕ (p = 1.000), and ICDAS grade (p = 0.305) were observed between T7 and T365 (ΔΕ12 = 3.4 (1.8/4.9)). Furthermore, at T365 four experienced dentists classified 55% and 39% of the lesions as "improved and no further treatment required" and "completely masked," respectively (Fleiss kappa: T365 = 0.851 (almost perfect)). CONCLUSION: Resin infiltration efficaciously masked post-orthodontic ICL 7 days and 12 months after treatment. These results for most of the teeth could not only be observed by quantitative but also by qualitative analysis. CLINICAL RELEVANCE: Resin infiltration efficaciously masks post-orthodontic initial carious lesions. The optical improvement can be observed directly after treatment and remains stable for at least 12 months.

Comprehensive Analysis of Scientific Output in Hip and Knee Arthroscopy.

PURPOSE OF THE STUDY A global bibliometric comparison of the level of scientific interest and output in the two research areas hip and knee arthroscopy (H-ASC and K-ASC) was carried out. In addition, the different degrees of publication activity in the countries and institutes performing this research were investigated. MATERIAL AND METHODS Publications from 1945-2020 listed in the Web of Science Core Collection were included in the study. Using the web application Science Performance Evaluation (SciPE), quantitative and qualitative aspects were evaluated. Subsequently, the date of publication, author information, and other metadata were analysed. RESULTS Since 1945, 3,924 studies have been published on K-ASC and 2,163 on H-ASC. The majority of the publications which have appeared since 2016 dealt with the topic of H-ASC (H-ASC: 241.2 publications/year; K-ASC: 217.4 publications/year). The USA published the most on both topics (H-ASC: 1,123 publications; K-ASC: 1,078 publications). More countries and institutes participated in K-ASC (3,008 institutes, 82 countries) than in H-ASC (103 institutes, 57 countries). The ten institutes with the most publications accounted for 36.71% and 12.34% of all publications on H-ASC and K-ASC, respectively. H-ASC received 78.12% of its funding from private sponsors while K-ASC was supported mainly by governmental/nonprofit sponsors (70.92%). CONCLUSIONS This study provides the first scientific comparison between H-ASC and K-ASC. Measured by qualitative and quantitative aspects, K-ASC was the most flourishing research area overall. In the last ten to five years, interest has shifted towards HASC with an increasing number of publications and a higher rate of citations. Key words: knee arthroscopy, hip arthroscopy, bibliometric comparison.

Coherent Modulation of Quasiparticle Scattering Rates in a Photoexcited Charge-Density-Wave System.

We present a complementary experimental and theoretical investigation of relaxation dynamics in the charge-density-wave (CDW) system TbTe_{3} after ultrafast optical excitation. Using time- and angle-resolved photoemission spectroscopy, we observe an unusual transient modulation of the relaxation rates of excited photocarriers. A detailed analysis of the electron self-energy based on a nonequilibrium Green's function formalism reveals that the phase space of electron-electron scattering is critically modulated by the photoinduced collective CDW excitation, providing an intuitive microscopic understanding of the observed dynamics and revealing the impact of the electronic band structure on the self-energy.

Effects of Different Optical Properties of Head Tissues on Near-Infrared Spectroscopy Using Monte Carlo Simulations.

In near-infrared spectroscopy (NIRS), it is crucial to have an accurate and realistic model of photon transport in the adult head for obtaining accurate brain oxygenation values. There are several studies on the influence of thickness, the morphology of extracerebral layers, and source-detector distance on the sensitivity of NIRS to the brain. However, the optical properties of the different layers vary between different publications. How is the performance of NIRS affected when the real optical properties differ from the assumed ones?We aim to investigate the influence of variation in scattering and absorption in a five-layered head model (scalp, skull, CSF, grey and white matter). We performed Monte Carlo simulations focusing on a five-layered slab mesh. The range of optical properties is based on a review of the published literature. We assessed the effect on light propagation by measuring the difference in the mean partial path lengths, attenuation, and the number of the detected photons between the different optical properties performing Monte Carlo simulations. For changes in the reduced scattering, we found that the upper layers tend to have a negative impact. In contrast, changes in lower layers tend to impact the brain's influence metrics positively. Furthermore, for small source-detector distances, the relative percentage difference between lower and higher values is greater than larger distances. Conclusions: We conclude that the assumption of different optical properties has a substantial effect on the sensitivity to the brain. This means that it is important to determine the correct optical properties for NIRS measurements in vitro and in vivo.

Cross-Frequency Coupling Between Brain and Body Biosignals: A Systemic Physiology Augmented Functional Near-Infrared Spectroscopy Hyperscanning Study.

BACKGROUND: Understanding the brain and body processes during interaction or cooperation between two or more subjects is an important topic in current neuroscientific research. In a previous study, we introduced a novel approach that enables investigation of the coupling of biosignals (brain and systemic physiology, SP) from two subjects: systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) hyperscanning. AIM: The aim was to extend our signal analysis approach by the cross-frequency time-dependent wavelet transform coherence (WTC) of the fNIRS and SP biosignals to gain new insights into the nature and cause of functional hyperconnectivity. SUBJECTS AND METHODS: 24 pairs of adults took part in a closed-eye versus prolonged eye-contact task of 10 min each. Brain and body activity was measured continuously by SPA-fNIRS hyperscanning. We calculated the time-dependent WTC of the biosignals for four different frequency bands: very low-frequency band (VLF, 0.002-0.08 Hz), low-frequency band 1 (LF1, 0.015-0.15 Hz), low-frequency band 2 (LF2, 0.08-0.15 Hz) and heart rate band (HR, 1-2 Hz). We then performed the cross-frequency correlated-coherence coupling analysis. RESULTS: A stronger cross-frequency coupling during the eye-contact condition (between 99 pairs of biosignals) was found than during the eye-closed condition (between 50 pairs of biosignals). Prolonged eye contact led to entrainment of the brain and body between different frequency bands and two subjects. The strongest hyperconnectivity was between the LF1-VLF frequency band. DISCUSSION AND CONCLUSION: With this exploratory study, we reveal further benefits of the SPA-fNIRS approach for future hyperscanning studies.

Machine Learning Distinguishes Familiar from Unfamiliar Pairs of Subjects Performing an Eye Contact Task: A Systemic Physiology Augmented Functional Near-Infrared Spectroscopy Hyperscanning Study.

BACKGROUND: Eye contact is an important aspect of human communication and social interactions. Changes in brain and systemic physiological activity associated with interactions between humans can be measured with systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) hyperscanning, enabling inter-brain and inter-body synchronisation to be determined. In a previous study, we found that pairs of subjects that are socially connected show higher brain and body synchrony. AIM: To enable a deeper understanding, our aim was to build and automatically detect the best set of features to distinguish between two different groups (familiar and unfamiliar pairs). MATERIAL AND METHODS: We defined several features based on the Spearman correlation and wavelet transform coherence (WTC) of biosignals measured on 23 pairs of subjects (13 familiar and 10 unfamiliar pairs) during eye contact for 10 min. Additional custom features that identify the maximum brain-to-body coupling instants between pairs were generated. RESULTS: After testing on combinations of different feature extraction methods, four subsets of features with the strongest discrimination power were taken into account to train a decision tree (DT) machine learning (ML) algorithm. We have obtained 95.65% classification accuracy using a leave-one-out cross-validation. The coupling features which represent the two maximum mean values resulting from the sum of 7 time-dependent WTC signals (oxyhaemoglobin concentration of the right prefrontal region, total haemoglobin concentration of the left and right prefrontal region, heart rate, electrodermal activity on the left and right wrist, and skin temperature on the right wrist) played an essential role in the classification accuracy. CONCLUSION: Training the DT-ML algorithm with combined brain and systemic physiology data provided higher accuracy than training it only with brain or systemic data alone. The results demonstrate the power of the SPA-fNIRS hyperscanning approach and the potential in applying ML to investigate the strength of social bonds in a wide range of social interaction contexts.

Development and Validation of Robust and Cost-Effective Liquid Heterogeneous Phantom for Time Domain Near-Infrared Optical Tomography.

Diffused light imaging techniques, such as near-infrared optical tomography (NIROT), require a stable platform for testing and validation that imitates tissue optical properties. The aim of this work was to build a robust, but flexible liquid phantom for BORL time-domain NIROT system Pioneer. The phantom was designed to assess penetration depth and resolution of the system, and to provide a heterogeneous inner structure that can be changed in controllable manner with adjustable optical properties. We used only in-house produced 3D-printed elements and mechanics of a budget 3D-printer to build the phantom, and managed to keep the overall costs below $500. We achieved stable and repeatable movement of an arbitrary structure in 3+1 degree of freedom inside the phantom and demonstrated its performance in a series of tests. Thus, we presented a universal and cost-effective solution for testing NIROT, that can be easily customised to various systems or testing paradigms.

Assessment of binocular fixational eye movements including cyclotorsion with split-field binocular scanning laser ophthalmoscopy.

Fixational eye movements are a hallmark of human gaze behavior, yet little is known about how they interact between fellow eyes. Here, we designed, built and validated a split-field binocular scanning laser ophthalmoscope to record high-resolution eye motion traces from both eyes of six observers during fixation in different binocular vergence conditions. In addition to microsaccades and drift, torsional eye motion could be extracted, with a spatial measurement error of less than 1 arcmin. Microsaccades were strongly coupled between fellow eyes under all conditions. No monocular microsaccade occurred and no significant delay between microsaccade onsets across fellow eyes could be detected. Cyclotorsion was also firmly coupled between both eyes, occurring typically in conjugacy, with gradual changes during drift and abrupt changes during saccades.

Bridging Theories for Ecosystem Stability Through Structural Sensitivity Analysis of Ecological Models in Equilibrium.

Ecologists are challenged by the need to bridge and synthesize different approaches and theories to obtain a coherent understanding of ecosystems in a changing world. Both food web theory and regime shift theory shine light on mechanisms that confer stability to ecosystems, but from different angles. Empirical food web models are developed to analyze how equilibria in real multi-trophic ecosystems are shaped by species interactions, and often include linear functional response terms for simple estimation of interaction strengths from observations. Models of regime shifts focus on qualitative changes of equilibrium points in a slowly changing environment, and typically include non-linear functional response terms. Currently, it is unclear how the stability of an empirical food web model, expressed as the rate of system recovery after a small perturbation, relates to the vulnerability of the ecosystem to collapse. Here, we conduct structural sensitivity analyses of classical consumer-resource models in equilibrium along an environmental gradient. Specifically, we change non-proportional interaction terms into proportional ones, while maintaining the equilibrium biomass densities and material flux rates, to analyze how alternative model formulations shape the stability properties of the equilibria. The results reveal no consistent relationship between the stability of the original models and the proportionalized versions, even though they describe the same biomass values and material flows. We use these findings to critically discuss whether stability analysis of observed equilibria by empirical food web models can provide insight into regime shift dynamics, and highlight the challenge of bridging alternative modelling approaches in ecology and beyond.

The Clinical Outcome of Custom-Made Implants in Primary and Revision Hip Arthroplasty.

PURPOSE OF THE STUDY Facing the increasing number of priary and revision hip arthroplasties, the therapy of complex osseus defects becomes a crucial issue. Large acetabular defects cannot be treated with standard implant. Individual, customized implants based on 3D computed tomography (CT) scans are used for reconstruction. However, high complication and revision rates come along with final favorable outcomes. MATERIAL AND METHODS Eight patients underwent primary or revision total hip arthroplasty by an anterolateral surgical approach using patient matched implants based on 3D CT scans. Six patients with a Paprosky type IIIB acetabular defect, one patient with a nonunion acetabular and femoral neck fracture and one patient with a severe hip dysplasia were included. The clinical data and the Merle d'Aubigné score assessing the clinical outcome pre- and postoperatively were analyzed retrospectively. RESULTS Patient matched implants were used for eight patients (four male and four female). The mean Merle d'Aubigné score improved from 8.1 (range 2-11) pre-operatively to 13 (range 9-17) at the final follow-up (p < 0.01). Postoperative complications were recorded in 3 cases. CONCLUSIONS Customized implants of severe acetabular defects provide a solution with a favorable outcome. Nevertheless, dislocation presents a significant complication. A reduction of complications in order to achieve the optimal custome-made implant is desirable. Key words: revision arthroplasty, patient-matched implants, Paprosky IIIB defects, clinical outcome.

Mucosal Immunization with DTaP Confers Protection against Bordetella pertussis Infection and Cough in Sprague-Dawley Rats.

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis. The transition from a whole-cell pertussis vaccine (wP and DTP) to an acellular pertussis vaccine (aP, DTaP, and Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Overall, our goal was to evaluate the route of vaccination in the coughing rat model of pertussis. Immunity induced by both oral gavage and intranasal vaccination of aP in B. pertussis challenged rats over a 9-day infection was compared to intramuscular wP (IM-wP)- and IM-aP-immunized rats that were used as positive controls. Our data demonstrate that mucosal immunization of aP resulted in the production of anti-B. pertussis IgG antibody titers similar to IM-wP- and IM-aP-vaccinated controls postchallenge. IN-aP also induced anti-B. pertussis IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against B. pertussis-induced cough, whereas OG-aP immunization did not protect against respiratory distress. Mucosal immunization by both intranasal and oral gavage administration protected against acute inflammation and decreased bacterial burden in the lung compared to mock-vaccinated challenge rats. The data presented in this study suggest that mucosal vaccination with aP can induce a mucosal immune response and provide protection against B. pertussis challenge. This study highlights the potential benefits and uses of the coughing rat model of pertussis; however, further questions regarding waning immunity still require additional investigation.

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice.

Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (i.n.) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (phosphate-buffered saline [PBS]), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particles (IRI-1501). We utilized two study designs: short term (challenged 35 days after priming vaccination) and long term (challenged 6 months after boost). The short-term study demonstrated that immunization with i.n. vaccine candidates decreased the bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis-specific IgG antibodies in both the serum and lung and increased numbers of anti-B. pertussis IgG-secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the i.n. vaccines correlated with protection, suggesting that long-term antibody responses can be protective.

Reinvestigating the Coughing Rat Model of Pertussis To Understand Bordetella pertussis Pathogenesis.

Bordetella pertussis is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP, DTaP, and Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the reemergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. The emergence of genetically diverging strains, combined with waning aP vaccine efficacy, calls for reevaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged 7-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of B. pertussis infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole-body plethysmography. Onset of cough occurred between 2 and 4 days after B. pertussis challenge, averaging five coughs per 15 min, with peak coughing occurring at day 8 postinfection, averaging upward of 13 coughs per 15 min. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days postchallenge. The rats exhibited increased bronchial restriction following B. pertussis infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-B. pertussis IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between B. pertussis strains.

Influence of study design on effects of mask wearing on fMRI BOLD contrast and systemic physiology - A comment on Law et al. (2021).

In a study by Law and colleagues recently published in Neuroimage, the authors reported that wearing a surgical mask during an fMRI scan leads to a statistically significant subject-specific change (30%) in the baseline BOLD level in gray matter, although the response to a sensory-motor task was unaffected. An average increase in end-tidal CO2 of 7.4% was found when wearing a mask, despite little support in the literature for major effects of mask wearing on blood gas levels. We comment on these findings, point out a several relevant limitations of the study design and provide alternative interpretations of these data.

In Phantom Validation of Time-Domain Near-Infrared Optical Tomography Pioneer for Imaging Brain Hypoxia and Hemorrhage.

The neonatal brain is a vulnerable organ, and lesions due to hemorrhage and/or ischemia occur frequently in preterm neonates. Even though neuroprotective therapies exist, there is no tool available to detect the ischemic lesions. To address this problem, we have recently designed and built the new time-domain near-infrared optical tomography (TD NIROT) system - Pioneer. Here we present the results of a phantom study of the system performance. We used silicone phantoms to mimic risky situations for brain lesions: hemorrhage and hypoxia. Employing Pioneer, we were able to reconstruct accurately both position and optical properties of these inhomogeneities.

Probe Design Optimization for Time-Domain NIROT "Pioneer" System for Imaging the Oxygenation of the Preterm Brain.

In preterm infants, there is a risk of life-lasting impairments due to hemorrhagic/ischemic lesions. Our time-domain (TD) near-infrared optical tomography (NIROT) system "Pioneer" aims at detecting both disorders with high spatial resolution. Successfully tested on phantoms, "Pioneer" entered the phase of improvements and enhancements. The current probe (A-probe) was adapted for an optoacoustics instrument. A new probe (B-probe) optimized for TD measurements is required. Our aim is to determine the optimal arrangement of light sources in the B-probe to increase the sensitivity and the resolution of Pioneer and to improve the ability of the system to detect both ischemia and hemorrhage. To do this, we simulated TD-NIROT signals in NIRFAST, a MATLAB-based package used to model near-infrared light propagation through tissue. We used 16 × 16 detector array, with ~2.2 mm distance between the detectors. Light sources were arranged around the field of view (FoV). We performed forward simulations of light propagation through a "homogeneous case" (HC) tissue (µ's = 5.6 cm-1, µa = 0.07 cm-1). Next, we simulated light propagation through "inhomogeneous case" -tissue' (IC) tissue by adding ischemia (µa = µa · 2.5 cm-1) or hemorrhage (µa = µa · 50 cm-1) to HT as a spherical inclusion of 5 mm radius at different depths in the FoV center and identified the source location that provides the higher contrast on the FoV: maxi ∈ I (FoVContrastSOURCE). It was found that sources located closer to the FoV center generate greater contrast for late photons. This study suggests the light sources in B-probe should be closer to the FoV center. The higher sensitivity is expected to lead to a higher image quality.

[Changes in regulations regarding fitness to drive in psychiatric disorders in The Netherlands, 2010-2019]. / Veranderingen in regels over rijgeschiktheid bij psychiatrische stoornissen in Nederland, 2010-2019.

BACKGROUND: In the last decade, regulations regarding the fitness to drive in The Netherlands have been changed extensively. AIM: To describe the changes in the regulations, and to evaluate the consequences for daily practice. METHOD: Overview of changes in the regulations concerning the fitness to drive as published in the Dutch legislation announcements in the past 10 years. RESULTS: Important changes have been implemented regarding the regulations on fitness to drive in patients with affective disorders, psychotic disorders, dementia, ADHD and pervasive developmental disorders. CONCLUSION: Compared to 2010, the regulations concerning the fitness to drive in psychiatric disorders are less rigid, more balanced, and more evidence based. Therefore, it has become easier to inform and advise the patient on this topic.